Advances in our understanding of mechanisms of venous thrombus resolution

Abstract

Traditionally, venous thrombosis has been seen as the consequence of a regulated cascade of proteolytic steps leading to the polymerization of fibrinogen and fibrin crosslinking that is facilitated by platelets. A new view of thrombosis is providing a more integrated concept, with components of the vascular wall contributing to the vascular remodeling of thrombosis. Angiogenesis and inflammation are two key mechanisms that safeguard venous thrombus resolution and restitution of vascular patency after thrombosis. Disturbance of these processes leads to thrombus persistence and has potentially severe consequences for affected patients. Examples for clinical conditions associated with recurrent or persisting venous thrombosis are post-thrombotic syndrome or chronic thromboembolic pulmonary hypertension. Recently, studies using animal models of venous thrombosis have contributed to a better understanding of thrombus non-resolution that will eventually lead to modification of current treatment concepts. For example, recent data suggest that innate immunity is involved in the modification of thrombosis.

Immune Factors in Deep Vein Thrombosis Initiation

“…Consequently, the primary effort of translational research should focus on DVT prevention and in this review, we have therefore concentrated specifically on the mechanisms of venous thrombosis initiation. For readers interested in thrombus resolution we recommend the following reviews on the topic 12 , 13 .…”

Endothelial cells from pulmonary endarterectomy specimens possess a high angiogenic potential and express high levels of hepatocyte growth factor

“…Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension that is related to unresolved organizing clots and it is generally acknowledged that pulmonary endarterectomy (PEA) is the gold standard for CTEPH treatment. Various etiological factors, including infection, inflammation, genetic susceptibilities, and insufficient angiogenesis [1], have been discussed as important pathogenetic factors [2]. Poor angiogenesis detected in PEA tissue specimens also implies a poor prognosis in CTEPH patients [3].…”

New findings on venous thrombogenesis

“…Lastly, this review is limited in scope to mechanisms affecting the development and propagation of VT, and does not discuss mechanisms affecting thrombus resolution or the post-thrombotic syndrome. These are important components of VT pathology, and we direct the reader to excellent review articles focused on these topics (107,108). Additional investigation of the pathophysiologic mechanisms determining the rate of thrombus resolution and severity of post-thrombotic syndrome will improve treatment of VT patients after the onset of thrombosis.…”